Association of plasma lipid levels with Alzheimer’s disease and Lewy body disease biomarkers: a cross-sectional study

While an atherogenic lipid profile has been considered a risk factor for Alzheimer’s disease (AD) in midlife, recent studies have reported inverse or U-shaped associations with disease risk in both AD and Lewy body disease (LBD). In this cross-sectional study, we examined the associations between individual lipid components and multimodal biomarkers of AD and LBD. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) database was used to assess cerebrospinal fluid (CSF)-based AD biomarkers, whereas the Severance database enabled evaluation of both amyloid and dopaminergic imaging biomarkers. General linear models were constructed for z-transformed CSF phosphorylated tau/Aβ 42 ratio in the ADNI database, z-transformed global standardized uptake value ratio on 18 F-florbetaben PET (FBB-Z) and z-transformed striatal dopamine transporter uptake (DAT-Z) in the Severance database, and cognitive scores. Covariates were age, sex, education, lipid-lowering agent use, cognitive stage, and APOE4 status. Higher levels of z-transformed high-density lipoprotein (HDL-Z) were associated with AD biomarkers across databases. In the Severance database, lower z-transformed triglyceride (TG-Z) levels were associated with both increased FBB-Z and reduced DAT-Z. In cognitive analyses, higher HDL-Z levels were associated with lower memory performance, while TG-Z showed inverted U-shaped associations with memory and executive functiorify whether these associations are specifin in the ADNI database. These findings suggest that lipid fractions are differentially associated with neurodegenerative processes, with HDL more closely related to AD-related degeneration and TG reflecting both AD- and LBD-related neurodegeneration.